Figure 1

Spatial memory deficits displayed by Tg-APP/PS1 mice were improved by NIa expression. (A) Experimental design of Lenti-NIa injection and behavioral performance. Lenti-NIa was injected in Tg-APP/PS1 mice at 7 months of age and behavioral tests were started 15 days after the injection, for the two-week period, the sequence of which was the Morris water maze test (WM), passive avoidance test (PA), and marble burying test (MB). (B) Escape latency on a hidden platform of Tg-APP/PS1 mouse control (Tg-CON), Tg-APP/PS1 mice infused with Lenti-NIa (Tg+NIa), and their non-transgenic control (WT) in the Morris water maze test. Tg-APP/PS1 mice infused with Lenti-GFP are used as Tg-APP/PS1 mouse control (Tg-CON) throughout this work. Numbers of animals used: WT, 5 males and 5 females; Tg-CON, 5 males and 4 females; Tg+NIa, 5 males and 4 females. Two-way repeated measures ANOVA and Bonferroni post-hoc test: significant difference between animal groups [F_(2,204) = 19.77, P < 0.0001], significant effect of time [F_(4,204) = 32.94, P < 0.0001] and significant animal group × time interaction [F_(8,204) = 2.301, P < 0.05]. Data are presented as the means ± SEM. ^**denotes a difference between WT and Tg-CON at P < 0.01 at the indicated time point. Separate two-way repeated measures ANOVA for the data groups between Tg-CON and Tg+NIa showed significant effects of treatment (NIa) [F_(1,128) = 10.95, P < 0.01] and time [F_(4,128) = 14.10, P < 0.0001], but no significant treatment × time interaction [F_(4,128) = 0.8769, P = 0.4798]. Data are presented as the means ± SEM. (C) The percentage of time spent in the target quadrant in the spatial probe trial test. The dashed line represents the chance performance level (25%) at each quadrant. Tg-CON; Tg-APP/PS1 mouse control. Tg+NIa; Tg-APP/PS1 mice infused with Lenti-NIa. WT; non-transgenic control. Target (T), opposite (O), and adjacent quadrants (L, R) are depicted on the right panel. Two-way ANOVA and Bonferroni post-hoc test: no difference between animal groups [F_(2,96) = 0.0000, P = 1], but significant difference between zones [F_(3,96) = 14.92, P < 0.0001] and significant animal group × zone interaction [F_(6,96) = 3.997, P < 0.01]. ^* and ^** denote differences between indicated groups in the T zone, at P < 0.05 and P < 0.01, respectively. Data are presented as the means ± SEM. (D) The percentage of time spent in the center vs. periphery zones in the hidden platform version of the Morris water maze examined on day 5 (right panel). The center and periphery zones are depicted (left panels). The periphery zone is defined as the area between wall and the circle apart by 10-cm from the wall. Representative spatial navigations on the water maze pool for 30-sec period are presented for WT, Tg-CON, and Tg+NIa mice. One-way ANOVA and Newman-Keuls post-hoc test; significant difference between animal groups in the periphery zone [F_(2,24) = 8.693, P < 0.01] and in the center zone [F_(2,24) = 8.715, P < 0.01]. ^* and ^** denote differences between indicated groups at P < 0.05 and P < 0.01, respectively. Data are presented as the means ± SEM.